Abnormalities in connective tissue function due to decreased fibril tensile strength may be considered the common pathway for clinical expression of wide range of derangements in collagen biosynthesis. This may be detected biochemically as increased skin collagen extractability. In this proposal, patients with clinical phenotypes suggestive of abnormalities in collagen biosynthesis will be screened for increased collagen extractability by sequential extractions of skin in progressively more disruptive buffers and characterization of collagen chain type by SDS-acrylamide gel electrophoresis and "mini" column carboxymethylcellulose chromatography. Patients with abnormalities of screening will be studied for possible collagen biosynthetic abnormalities by fibroblast cultures and direct analysis of skin biopsies. The clinical phenotypes to be studied are patients with 1. Marfanoid habitus including: A. The Marfan Syndrome, B. Homocystinuria and C. Sickle Cell patients with Marfanoid Habitus and 2. Patients with variants of the Ehlers-Danlos Syndrome. In addition, further characterization of the mechanism of lysyl oxidase deficiency in X-Linked Cutis Laxa is proposed.